A goal of this research is to characterize hepatitis B Dane particles biochemically and determine whether they are the infectious form of hepatitis B virus (HBV). The structure of Dane particle DNA and the mechanism of the Dane particle DNA polymerase reaction involving the endogenous DNA will be studied, and attempts will be made to purify and chemically characterize the DNA polymerase. Dane particle DNA will be tested for infectivity in tissue culture. Radioactive Dane particle DNA will be used for DNA-DNA hybridization to test for homologous base sequences in the DNA of uninfected and hepatitis B virus infected liver, and in tissue involved with chronic active hepatitis and hepatoma. The peptide composition and arrangement in purified Dane particles, Dane particle cores and e antigen, and the antigenic and chemical structure of individual peptides will be studied. The relationship of e antigen to Dane particles and hepatitis B core antigen (HBcAg) will be determined. Attempts will be made to infect tissue culture cells with purified Dane particles to establish that they are infectious. Clinical studies will be done to investigate the occurrence of Dane particles in chronic HBcAg carriers and whether the levels of these particles correlate with the infectiousness of carriers. The immune response to hepatitis B antigens and the relationship of the immune response to disease will be studied.